Protective Effects of Mdivi-1 on Cognition Disturbance Following Sepsis in Mice via Alleviating Microglia Activation and Polarization.

Background: Neuroinflammation is one of the essential pathogeneses of cognitive damage suffering from sepsis-associated encephalopathy (SAE). Lots of evidences showed the microglia presented mitochondrial fragmentation during SAE. This study investigated the protective effects and novel mechanisms of inhibiting microglia mitochondrial fragmentation via mitochondrial division inhibitor 1 (Mdivi-1) on cognitive damage in SAE.

Kupffer-Cell-Targeted Carboxylesterase 1f Knockdown Deteriorates Lipopolysaccharide/D-Galactosamine-Induced Acute Liver Failure Through Regulating Cellular Polarization in Mice.

Aims: Carboxylesterase (Ces)1f is implicated in protection against hepatic inflammation, but it is unclear whether the enzyme has an influence in polarization of Kupffer cells (KCs), the innate immune cells mediating hepatic inflammatory injury including acute liver failure (ALF). In the present study, we aim to explore KC polarization induced by Ces1f in mice with lipopolysaccharide/D-galactosamine (LPS/D-GalN)-induced ALF. We adopted a novel delivery system, β-1,3-D-glucan-encapsulated Endoporter-siRNA particles, to specifically target KC Ces1f knockdown via tail vein injection in mice.

Role of Hippo/ACSL4 axis in ferroptosis-induced pericyte loss and vascular dysfunction in sepsis.

Sepsis is a critical condition characterized by a systemic inflammatory response to infection, often leading to severe vascular dysfunction and high mortality. One of the hallmarks of vascular dysfunction in sepsis is increased vascular permeability and the loss of pericytes, which are essential for maintaining vascular integrity. Despite the significance of pericyte loss in sepsis, the primary type of cell death responsible and the underlying molecular mechanisms remain incompletely understood.

Dexmedetomidine Ameliorates Myocardial Ischemia-Reperfusion Injury by Inhibiting MDH2 Lactylation via Regulating Metabolic Reprogramming.

Myocardial ischemia-reperfusion injury (MIRI) significantly worsens the outcomes of patients with cardiovascular diseases. Dexmedetomidine (Dex) is recognized for its cardioprotective properties, but the related mechanisms, especially regarding metabolic reprogramming, have not been fully clarified. A total of 60 patients with heart valve disease are randomly assigned to Dex or control group.

Unfractionated Heparin Enhances Sepsis Prognosis Through Inhibiting Drp1-Mediated Mitochondrial Quality Imbalance.

Unfractionated heparin (UFH) is commonly used as an anticoagulant in sepsis treatment and has recently been found to have non-anticoagulant effects, but underlying mechanisms remain unclear. This retrospective clinical data showed that UFH has significant protective effects in sepsis compared to low-molecular-weight heparin and enoxaparin, indicating potential benefits of its non-anticoagulant properties. Recombinant protein chip screening, surface plasmon resonance, and molecular docking data demonstrated that UFH specifically bound to the cytoplasmic Drp1 protein through its zone 2 non-anticoagulant segment.

The mitochondrial division inhibitor Mdivi-1 protected organ function and extended the treatment window in rats with uncontrolled haemorrhagic shock.

Aim: To elucidate whether the application of the mitochondrial division inhibitor Mdivi-1 can protect organ function and prolong the treatment window for traumatic hemorrhagic shock.

Methods: Before definitive haemostasis treatment, Mdivi-1 (0.25 mg/kg, 0.

Role of Excessive Mitochondrial Fission in Seawater Immersion Aggravated Hemorrhagic Shock-Induced Cardiac Dysfunction and the Protective Effect of Mitochondrial Division Inhibitor-1.

Seawater immersion significantly aggravated organ dysfunction following hemorrhagic shock, leading to higher mortality rate. However, the effective treatment is still unavailable in clinic. Mitochondria were involved in the onset and development of multiple organ function disorders; whether mitochondria participate in the cardiac dysfunction following seawater immersion combined with hemorrhagic shock remains poorly understood.

THE PROTECTIVE EFFECT OF FASCIOTOMY COMBINED WITH HYPERTONIC SALINE FLUSHING FOR CRUSH SYNDROME IN RATS.

In natural disasters such as earthquakes and landslides, the main problem that wounded survivors are confronted with is crush syndrome (CS). The aim of this study was to explore more convenient and effective early treatment measures for it. In the present study, we investigated the protective effect of fasciotomy combined with different concentration of hypertonic saline flushing with CS rats.

Protective Effects and Mechanisms of Inhibiting Endoplasmic Reticulum Stress on Cold Seawater Immersion Combined with Hemorrhagic Shock.

Purpose: Cold seawater immersion aggravates hemorrhagic shock-induced homeostasis imbalance and organ dysfunction, leading to increased mortality. Previous studies have shown that treatments targeting oxidative stress and mitochondrial dysfunction have limited efficacy for cold seawater immersion combined with hemorrhagic shock (SIHS). Thus, the mechanisms responsible for SIHS need further investigation.

Interleukin-1β stimulated macrophage derived exosomes improve myocardial injury in sepsis via regulation of mitochondrial homeostasis: Experimental research.

Background: The purpose of this study was to investigate the effects of interleukin-1β (IL-1β) stimulation on the protection of macrophage derived exosomes miR-146a (M-IL-exo-146a) on sepsis induced myocardial injury (SMI) in vitro and in vivo.

Methods: Macrophage derived exosomes (M-exo) and IL-1β stimulated macrophage exosomes (M-IL-exo) were isolated from macrophages of sepsis with or without IL-1β. The expressions of miR-146a in M-exo and M- IL-exo were detected by fluorescence quantitative PCR.

Corrigendum: Integrative single-cell RNA sequencing and metabolomics decipher the imbalanced lipid-metabolism in maladaptive immune responses during sepsis.

[This corrects the article DOI: 10.3389/fimmu.2023.

4-phenylbutyric acid improves sepsis-induced cardiac dysfunction by modulating amino acid metabolism and lipid metabolism via Comt/Ptgs2/Ppara.

Introduction: Cardiac dysfunction after sepsis the most common and severe sepsis-related organ failure. The severity of cardiac damage in sepsis patients was positively associated to mortality. It is important to look for drugs targeting sepsis-induced cardiac damage.

Notoginsenoside R1 improves intestinal microvascular functioning in sepsis by targeting Drp1-mediated mitochondrial quality imbalance.

Context: Sepsis can result in critical organ failure, and notoginsenoside R1 (NGR1) offers mitochondrial protection.

Objective: To determine whether NGR1 improves organ function and prognosis after sepsis by protecting mitochondrial quality.

Materials And Methods: A sepsis model was established in C57BL/6 mice using cecum ligation puncture (CLP) and an model with lipopolysaccharide (LPS, 10 µg/mL)-stimulated primary intestinal microvascular endothelial cells (IMVECs) and then determine NGR1's safe dosage.

Exosomes miRNA-499a-5p targeted CD38 to alleviate anthraquinone induced cardiotoxicity: experimental research.

Background: The purpose of this study was to investigate the effects of cardiac homing peptide (CHP) engineered bone marrow mesenchymal stem cells (BMMSc) derived exosomes (B-exo) loaded miRNA-499a-5p on doxorubicin (DOX) induced cardiotoxicity.

Methods: miRNA chip analysis was used to analyze the differences between DOX induced H9c2 cells and control group. CHP engineering was performed on BMMSc derived exosomes to obtain C-B-exo.

Radix Sanguisorbae Improves Intestinal Barrier in Septic Rats via HIF-1 α/HO-1/Fe Axis.

Objective: To investigate whether Radix Sanguisorbae (RS, Diyu) could restore intestinal barrier function following sepsis using a cecal ligation and puncture (CLP)-induced septic rat model and lipopolysaccharide (LPS)-challenged IEC-6 cell model, respectively.

Methods: Totally 224 rats were divided into 4 groups including a control, sham, CLP and RS group according to a random number table. The rats in the control group were administrated with Ringer's lactate solution (30 mL/kg) with additional dopamine [10 µ g/(kg·min)] and given intramuscular injections of cefuroxime sodium (10 mg/kg) 12 h following CLP.

Metabolomics and machine learning approaches for diagnostic and prognostic biomarkers screening in sepsis.

Background: Sepsis is a life-threatening disease with a poor prognosis, and metabolic disorders play a crucial role in its development. This study aims to identify key metabolites that may be associated with the accurate diagnosis and prognosis of sepsis.

Methods: Septic patients and healthy individuals were enrolled to investigate metabolic changes using non-targeted liquid chromatography-high-resolution mass spectrometry metabolomics.

Activated Drp1 Initiates the Formation of Endoplasmic Reticulum-Mitochondrial Contacts via Shrm4-Mediated Actin Bundling.

Excessive mitochondrial fission following ischemia and hypoxia relies on the formation of contacts between the endoplasmic reticulum and mitochondria (ER-Mito); however, the specific mechanisms behind this process remain unclear. Confocal microscopy and time course recording are used to investigate how ischemia and hypoxia affect the activation of dynamin-related protein 1 (Drp1), a protein central to mitochondrial dynamics, ER-Mito interactions, and the consequences of modifying the expression of Drp1, shroom (Shrm) 4, and inverted formin (INF) 2 on ER-Mito contact establishment. Both Drp1 activation and ER-Mito contact initiation cause excessive mitochondrial fission and dysfunction under ischemic-hypoxic conditions.

Neutrophil membrane-engineered Panax ginseng root-derived exosomes loaded miRNA 182-5p targets NOX4/Drp-1/NLRP3 signal pathway to alleviate acute lung injury in sepsis: experimental studies.

Background: The purpose of this study was to prepare neutrophil membrane-engineered Panax ginseng root-derived exosomes (N-exo) and investigate the effects of N-exo microRNA (miRNA) 182-5p (N-exo-miRNA 182-5p) on acute lung injury (ALI) in sepsis.

Methods: Panax ginseng root-derived exosomes were separated by differential centrifugation. Neutrophil membrane engineering was performed on exo to obtain N-exo.

L-Arginine, as an essential amino acid, is a potential substitute for treating COPD via regulation of ROS/NLRP3/NF-κB signaling pathway.

Backgrounds: Chronic obstructive pulmonary disease (COPD) is a frequent and common disease in clinical respiratory medicine and its mechanism is unclear. The purpose of this study was to find the new biomarkers of COPD and elucidate its role in the pathogenesis of COPD. Analysis of metabolites in plasma of COPD patients were performed by ultra-high performance liquid chromatography (UPLC) and quadrupole time-of-flight mass spectrometry (TOF-MS).

VDAC2 malonylation participates in sepsis-induced myocardial dysfunction via mitochondrial-related ferroptosis.

Sepsis-induced myocardial dysfunction (SIMD) is a prevalent and severe form of organ dysfunction with elusive underlying mechanisms and limited treatment options. In this study, the cecal ligation and puncture and lipopolysaccharide (LPS) were used to reproduce sepsis model and vivo. The level of voltage-dependent anion channel 2 (VDAC2) malonylation and myocardial malonyl-CoA were detected by mass spectrometry and LC-MS-based metabolomics.

Effects of Mdivi-1 on Extending the Golden Treatment Time following Hemorrhagic Shock in Hot Environment in Rats.

It is found that a hot environment aggravates hemorrhagic shock-induced internal environment and organ dysfunction. Meanwhile mitochondria show over-fission. Whether inhibition of mitochondrial fission benefits from the early treatment of hemorrhagic shock under a hot environment is unclear.